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Stockholders' Equity (Tables)

12 Months Ended

Dec. 31, 2018

Equity [Abstract]

Schedule of Accounting for Share-Based Compensation

The following table summarizes share-based compensation expense (in thousands):

			December 31,
			2018						2017						2016
Share-based compensation expense as a component of:
Research and development expenses			$	8,352					$	14,235					$	8,836
General and administrative expenses			12,494						10,680						10,057
			$	20,846					$	24,915					$	18,893

Schedule of Stock Option Plan Activity

Following is a summary of our stock option plan activity and related information:

			Shares						Weighted Average Exercise Price						Weighted Average Remaining Contractual Term in Years						Aggregate Intrinsic Value (In  thousands)
Balance at December 31, 2017			1,876,332						$	53.17					5.77						$	157,340
Granted			228,362						162.00
Exercised			(358,162)						55.24
Forfeited			(10,228)						114.53
Balance at December 31, 2018			1,736,304						66.71						5.47						125,858
Exercisable at December 31, 2018			1,313,374						47.03						4.56						117,314
Options vested and expected to vest as of December 31, 2018			1,734,304						$	66.71					5.47						$	125,858

Schedule of Stock Option Plan Activity by Exercise Price Range

Following is a further breakdown of the options outstanding as of December 31, 2018:

Range of exercise prices			Options outstanding						Weighted average remaining  life in years						Weighted average exercise price						Options exercisable						Weighted average exercise price
$8.58 - $10.05			184,702						1.87						$	10.00					184,702						$	10.00
$10.12 - $12.81			46,510						2.92						11.40						46,510						11.40
$14.47 - $14.47			217,616						3.11						14.47						203,616						14.47
$16.14 - $17.88			38,790						0.17						16.36						38,790						16.36
$21.92 - $21.92			200,372						4.13						21.92						200,372						21.92
$32.00 - $56.26			182,767						5.70						50.38						174,470						50.10
$63.58 - $67.53			20,434						5.44						67.42						20,153						67.47
$74.42 - $74.42			190,825						5.12						74.42						190,825						74.42
$85.79 - $100.38			299,282						7.57						93.32						157,872						91.62
$101.15 - $195.91			353,006						8.79						148.50						96,064						131.77
			1,734,304						5.47						$	66.71					1,313,374						$	47.03

Schedule of Stock Option Weighted-Average Assumptions

The assumptions used for the specified reporting periods and the resulting estimates of weighted-average grant date fair value per share of options granted:

			Year Ended December 31,
			2018						2017						2016
Risk-free interest rate			2.7%-3.0%						2.0%-2.2%						1.3%-1.9%
Expected volatility			33%-36%						43%-47%						48%-50%
Expected term			5.1 to 5.8 years						6.5 to 6.8 years						6.6 to 6.7 years

Schedule of Restricted Stock Activity

The following is a summary of our restricted stock activity and related information:

			Shares						Weighted-Average Grant Date Fair Value
Outstanding at December 31, 2017			133,294						$	91.60
Granted			62,133						169.92
Vested			(61,989)						86.19
Forfeited			(1,165)						125.16
Outstanding at December 31, 2018			132,273						$	130.63

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